Effects of aging on event-related neural activity related to prospective memory

The neural foundation of age-related declines in prospective memory was explored using event-related brain potentials (ERPs). Consistent with previous research, a decline in the efficiency of prospective memory was observed in older adults that reflected a decrease in veridical prospective responses and an increase in false prospective responses. The neurophysiological data revealed an age-related reduction in the amplitude of modulations of the ERPs related to prospective remembering, but not visual information processing, and are consistent with the hypothesis that a reduction in the efficiency of a frontally mediated neural system contributes to prospective memory failure in older adults.     

Neural correlates of prospective memory across the lifespan

OVERVIEW: Behavioural data reveal an inverted U-shaped function in the efficiency of prospective memory from childhood to young adulthood to later adulthood. However, prior research has not directly compared processes contributing to age-related variation in prospective memory across the lifespan, hence it is unclear whether the same factors explain the 'rise and fall' of prospective remembering from childhood to later adulthood. The present study examined this question using a paradigm that allowed us to consider the behavioural and neural correlates of processes associated with the prospective and retrospective components of prospective memory. METHODS: We compared 14 adolescents, 14 young adults, and 14 old adults in a paradigm where the prospective memory task was embedded in a semantic categorization task. RESULTS: The behavioural data revealed an inverted U-shaped function with adolescents and old adults performing poorly relative to young adults. Analyses of the error data revealed that different processes may have contributed to failures of prospective memory in adolescents and older adults. This finding was supported by age differences in ERP-components for cue detection and post-retrieval processes. Additionally, source localization using LORETA revealed different patterns of neural recruitment for adolescents and older adults relative to younger adults. CONCLUSION: Our findings demonstrate that adolescents and older adults show different patterns of behavioural errors and neural recruitment for successful prospective remembering indicating that different processes may contribute to the 'rise and fall' of prospective memory across the lifespan.     

Dissociative contributions of medial temporal and frontal regions to prospective remembering

Prospective memory is memory of future intentions or plans in everyday life. Although some previous neuropsychological studies have stated that the prefrontal cortex and the medial temporal lobe are essential for successful prospective remembering, how the two regions contribute to prospective remembering remains unclear. We therefore used prospective memory training in the present study to investigate the neural mechanism of two components of prospective remembering: remembering to remember and remembering content. Two brain-damaged patients participated in this study: patient Y.O., who had lesions in the medial temporal lobe bilaterally, and patient T.K., who had a lesion in the basal forebrain and right medial frontal lobe. Both participants exhibited a severe anterograde amnesic syndrome and had normal IQ scores. Before the prospective memory training the participants underwent several index memory tests to examine their general memory and prospective memory performance. The training consisted of requesting the participants to perform an original mini-day task, in which they were first asked to memorize five simple daily actions with their times for execution, and then to recall the content of the actions when shown a drawing of a clock showing the proper time for execution. A training session was carried out once a week for 3 months. After completing training, the participants were again requested to take the same index memory tests. The results of the training task showed that Y.O.'s memory performance had gradually improved across all sessions of training, but T.K.'s improvement was not as marked. A more detailed analysis revealed that Y.O.'s memory performance was better for recalling time than for recalling content, whereas T.K.'s memory performance was better for recalling content than for recalling time. Furthermore, the results of the final index memory tests showed that the only improvement in Y.O.'s prospective memory was in remembering to remember, and that the only improvement in T.K.'s prospective memory was in remembering content. These results provide strong evidence that these two remembering components of prospective memory have independent neural bases, with the basal forebrain and right medial frontal lobe being required for remembering to remember, and the medial temporal lobe being required for remembering content. The results also suggest that memory training is an effective, means of improving everyday memory.     

Differential components of prospective memory? Evidence from fMRI

Two of the principal components of prospective memory (i.e., remembering to carry out delayed intentions) are recognizing the appropriate context to act ("cue identification") and remembering the action to be performed ("intention retrieval"). In this experiment, the demands on these components were manipulated while measuring brain activity using fMRI to explore whether the two components share a common neural basis. The results showed significant behavioral differences between the cue identification and intention retrieval conditions. However, a consistent pattern of hemodynamic changes was found in both prospective memory conditions in anterior prefrontal cortex (BA 10), with lateral BA 10 activation accompanied by medial BA 10 deactivation. These effects were more pronounced when demands on intention retrieval were high. This is consistent with the hypothesis that anterior prefrontal cortex (area 10) supports the biasing of attention between external events (e.g., identifying the cue amid distracting stimuli) and internal thought processes (i.e., maintaining the intention and remembering the intended actions). Together, the results suggest that whilst cue identification and intention retrieval may be behaviorally separable, they share at least some common neural basis in anterior prefrontal cortex.     

Planning and realisation of complex intentions in patients with Parkinson's disease

BACKGROUND: There is some evidence that patients with Parkinson's disease may impaired in prospective memory performance (planning and self initiated realisation of delayed intentions). Little is known about the effect of the disease on distinct phases of prospective memory and the potential mechanisms underlying these effects. OBJECTIVE: To investigate intention formation, intention retention, intention initiation, and intention execution of patients with Parkinson's disease and test for the mediating influence of working memory, inhibition, short term retrospective memory, and divided attention. METHODS: 16 patients with Parkinson's disease and 16 age and education matched normal controls were given a complex event based prospective memory task which differentiates four phases of prospective remembering. In addition, participants completed tasks assessing potential cognitive mediators. RESULTS: On the prospective remembering task, Parkinson patients were impaired in the intention formation phase and showed a trend towards impairment in the intention initiation. In contrast, there were no impairments of retrospective intention retention or the fidelity with which the patients executed their previously developed plan. The group effects were related to interindividual differences in working memory span. CONCLUSIONS: The results suggest that the planning phase of prospective remembering is specifically impaired in Parkinson's disease, and that the impairment is related to working memory deficit. In contrast, even when complex intentions have to be remembered, the retrospective storage of intentions to be performed is not impaired.     

Deficits in prospective memory following damage to the prefrontal cortex

Neuropsychological investigations of prospective memory (PM), representing memory of future intentions or plans, have evolved over the past two decades. The broadly accepted divisions involved in PM consist of a prospective memory component (PMC), a process for remembering to remember, and a retrospective memory component, a process for remembering the content of the intended action. Previous functional neuroimaing studies have provided some evidence that the rostral prefrontal cortex (BA10) is one of areas that is critical for prospective remembering. However, the question of whether damage to part of the prefrontal cortex affects attenuated performance for PMC remains unresolved. In this study, 74 participants with traumatic brain injury (TBI) including focal damage to frontal or temporal lobe areas were administered thirteen standard neuropsychological tests and the PM task. To identify influential areas contributing to PM performance, discriminant function analysis was conducted. The results indicated that the following three areas are highly contributory to PM performance: the right dorsolateral prefrontal cortex; the right ventromedial prefrontal cortex; and the left dorsomedial prefrontal cortex. Comparing differences in neuropsychological test scores showed that orientation scores were significantly higher in the greater PM performance group, suggesting that PMC represents an integrated memory function associated with awareness of current status. These data contribute to our understanding of the neural substrates and functional characteristics of the PMC.     

The effects of old age and distraction on the assessment of prospective memory in a simulated naturalistic environment

BACKGROUND: The ability to remember to complete future intentions, prospective memory, often begins to fail in old age. The aim of the present study was to examine the sensitivity of a computer-based procedure using naturalistic stimuli to age-related increases in forgetting under conditions of high (increased visual and auditory noise) or low distraction. METHODS: Participants were tested in a virtual shopping precinct constructed from linked photographs, sounds, and video segments. Groups of 32 older and younger persons completed two concurrent memory tasks while moving along the street. In one task, participants were given errands to complete with an accessible checklist, in the other, they were required to remember to respond to three different targets that appeared repeatedly. RESULTS: The results confirmed previous findings that older adults have difficulty remembering future intentions, even on a self-paced task using naturalistic stimuli, and showed that this was accentuated in noisy environments. CONCLUSIONS: Older persons have particular difficulty remembering in noisy environments, and results from testing in the clinic may underestimate the practical memory problems experienced by older adults with mild cognitive impairments. The findings provide encouragement for the construction of computer-generated environments to measure functional deficits in cognition.     

Early episodic memory impairments in Alzheimer's disease

Patients with Alzheimer's disease (AD) show early episodic memory impairments. Such deficits reflect specific impairments affecting one or several stages of encoding, storage and retrieval processes. However, AD patients not only have great difficulty retrieving memories and information but also suffer from distortions of memory, as intrusions and false recognitions. Intrusions can be defined as the unintentional recall of inappropriate information in a laboratory-learning tasks such as word-list recall and story recall. False recognition refers to the erroneous recognition of information that was not previously presented. The first objective of this review is to present studies from the literature that allowed a better understanding of the nature of episodic memory deficits in AD, and to examine recent research on false memories. The second part of this review is aimed at presenting recent research conducted on prospective memory (PM) in Alzheimer's disease. Prospective memory situations involve forming intentions and then realizing those intentions at some appropriate time in the future. Everyday examples of prospective memory include remembering to buy bread on the way home from work, remembering to give friends a message upon next encountering them, and remembering to take medication. Patients suffering from AD show difficulties in performing prospective tasks in daily life, according to the complaints of their care givers, and these difficulties are massively present at the first stages of the disease. Nevertheless, very few studies have been dedicated to this subject, although the evaluation of PM could be helpful for the early diagnosis of AD.     

Prospective memory in adults with high-functioning autism spectrum disorders: Exploring effects of implementation intentions and retrospective memory load

This study examined, for the first time, the impact of implementation intentions on prospective memory (PM) performance in adults with autism spectrum disorders (ASD) and further explored the role of retrospective memory for PM in ASD. PM was assessed with Virtual Week, a computerized game simulating upcoming everyday-life tasks. Twenty-seven adults with ASD and 27 age- and ability-matched controls were included. Half of the participants were instructed to form implementation intentions (i.e., encoding PM tasks in form of if-then statements), while the rest received simple PM instructions. Results provide first tentative evidence for beneficial effects of implementation intentions and PM tasks with low demands on retrospective memory for adults with ASD's PM. Overall, results point to the importance of planning and retrospective memory for successful prospective remembering in ASD.     

The effects of aging on controlled attention and conflict processing in the Stroop task

Recent computational modeling and behavioral work indicate that age-related declines in the ability to represent task context may contribute to disruptions of working memory and selective attention in older adults. However, it is unclear whether age-related declines in context processing arise from a disruption of the encoding or maintenance of task context and how age-related declines in context processing interact with mechanisms supporting conflict detection and resolution processes contributing to efficient selection of task-relevant information. This study examines the effects of aging on the neural correlates of context and conflict processing in the Stroop task using event-related brain potentials (ERPs). Age-related differences in the time course of modulations of the ERPs associated with encoding (P3) and maintaining (slow wave) task context were observed. There were also age-related differences in the N450, conflict SP, and ERN associated with conflict processing that interacted with task context. These data indicate that aging is associated with declines in the efficiency of those neural mechanisms supporting both context and conflict processing, and that the effects of aging are not pervasive but rather interact with task context.     

Modulation of a fronto-parietal network in event-based prospective memory: an rTMS study

Event-based prospective memory (PM) is a multi-component process that requires remembering the delayed execution of an intended action in response to a pre-specified PM cue, while being actively engaged in an ongoing task. Some neuroimaging studies have suggested that both prefrontal and parietal areas are involved in the maintenance and realization of delayed intentions. In the present study, transcranial magnetic stimulation (TMS) was used to investigate the causal involvement of frontal and parietal areas in different stages of the PM process (in particular, target checking and intention retrieval), and to determine the specific contribution of these regions to PM performance.Our results demonstrate that repetitive TMS (rTMS) interferes with prospective memory performance when applied at 150-350 ms to the right dorsolateral prefrontal cortex (DLPFC), and at 400-600 ms when applied to the left posterior parietal cortex (PPC).The present study provides clear evidence that the right DLPFC plays a crucial role in early components of the PM process (target checking), while the left PPC seems to be mainly involved in later processes, such as the retrieval of the intended action.     

Memory encoding and aging: a neurocognitive perspective

This review article surveys the evidence for age-related changes in memory from cognitive and neuroimaging studies. It is probable that the observed declines in episodic memory with increasing age are a consequence of impairments in both acquisition (encoding) and retrieval - possibly for similar reasons - but the present review focuses on the former set of processes. An additional emphasis is on a processing approach to understanding age-related encoding deficiencies; we suggest that many problems stem from a decline in the ability to self-initiate deeper semantic processing operations. The article briefly discusses the role of declining sensory and perceptual abilities, but focuses primarily on the nature of processing resources, their consequences for memory acquisition, and on age-related changes in cognition and neural functioning. We also survey the evidence for neuroplasticity in the older brain, and how compensatory activities at behavioral and neural levels can reduce age-related problems. Finally, we review recent studies of brain and cognitive training procedures. Age-related memory problems are real, but there are also grounds for optimism.     

Age-related differences in the neural correlates of remembering time-based intentions

The present study used event-related potentials (ERPs) to explore the effect of age on the neural correlates of monitoring processes involved in time-based prospective memory. In both younger and older adults, the addition of a time-based prospective memory task to an ongoing task led to a sustained ERP activity broadly distributed over the scalp. Older adults, however, did not exhibit the slow wave activity observed in younger adults over prefrontal regions, which is considered to be associated with retrieval mode. This finding indicates that age-related decline in intention maintenance might be one source of the impaired prospective memory performance displayed by older adults. An 'anterior shift' in scalp distribution of the P3 was observed in older adults, and was related to lower levels of accuracy in prospective memory performance. This relationship suggests that possible factors responsible for age-related decline in prospective memory performance include the decreased efficiency of executive/frontal functions as well as the reduced amount of resources available for the prospective memory task.     

The effects of working memory demands on the neural correlates of prospective memory

Event-related brain potentials (ERPs) were used to examine the reciprocal costs of working and prospective memory loads on the neural correlates of the realization of delayed intentions and the detection of target stimuli. The electrophysiological data revealed several interesting results: (1) distinct modulations of the ERPs were elicited by working memory targets and prospective memory cues, (2) working memory load modulated the amplitude of the N300 elicited by prospective memory cues, (3) prospective memory load was associated with a broadly distributed sustained modulation that began shortly after stimulus onset, and (4) brain-behavior correlations between the neural correlates of prospective memory and working memory varied with the working memory demands of the ongoing activity. These findings appear to indicate that attentional processes associated with the detection of prospective memory cues are sensitive to the working memory demands of the ongoing activity and that different processes may support prospective memory depending on the working memory demands of the ongoing activity.     

Theta synchronization during episodic retrieval: neural correlates of conscious awareness

The neural correlates of conscious awareness during successful memory retrieval were examined. In a recognition test, subjects indicated whether they consciously recalled the event in which a word was earlier presented (Remembering), or whether they recognized it on the basis that it was familiar in the absence of recollection (Knowing). An early EEG synchronization in the theta band predicted knowing, and a later remembering. Moreover, early and late event-related potentials were also found to predict knowing and remembering, respectively. The results indicate that the temporal dynamics of theta synchronization are related to the particular conscious experiences associated with memory retrieval.     

Prospective coding for objects in primate prefrontal cortex.

We examined neural activity in prefrontal (PF) cortex of monkeys performing a delayed paired associate task. Monkeys were cued with a sample object. Then, after a delay, a test object was presented. If the test object was the object associated with the sample during training (i.e., its target), they had to release a lever. Monkeys could bridge the delay by remembering the sample (a sensory-related code) and/or thinking ahead to the expected target (a prospective code). Examination of the monkeys' behavior suggested that they were relying on a prospective code. During and shortly after sample presentation, neural activity in the lateral PF cortex primarily reflected the sample. Toward the end of the delay, however, PF activity began to reflect the anticipated target, which indicated a prospective code. These results provide further confirmation that PF cortex does not simply buffer incoming visual inputs, but instead selectively processes information relevant to current behavioral demands, even when this information must be recalled from long-term memory.     

When keeping in mind supports later bringing to mind: neural markers of phonological rehearsal predict subsequent remembering.

The ability to bring to mind a past experience depends on the cognitive and neural processes that are engaged during the experience and that support memory formation. A central and much debated question is whether the processes that underlie rote verbal rehearsal-that is, working memory mechanisms that keep information in mind-impact memory formation and subsequent remembering. The present study used event-related functional magnetic resonance imaging (fMRI) to explore the relation between working memory maintenance operations and long-term memory. Specifically, we investigated whether the magnitude of activation in neural regions supporting the on-line maintenance of verbal codes is predictive of subsequent memory for words that were rote-rehearsed during learning. Furthermore, during rote rehearsal, the extent of neural activation in regions associated with semantic retrieval was assessed to determine the role that incidental semantic elaboration may play in subsequent memory for rote-rehearsed items. Results revealed that (a) the magnitude of activation in neural regions previously associated with phonological rehearsal (left prefrontal, bilateral parietal, supplementary motor, and cerebellar regions) was correlated with subsequent memory, and (b) while rote rehearsal did not--on average--elicit activation in an anterior left prefrontal region associated with semantic retrieval, activation in this region was greater for trials that were subsequently better remembered. Contrary to the prevalent view that rote rehearsal does not impact learning, these data suggest that phonological maintenance mechanisms, in addition to semantic elaboration, support the encoding of an experience such that it can be later remembered.     

Forming intentions successfully: Differential compensational mechanisms of adolescents and old adults

Introduction

Forming an intention is a key aspect of prospective memory, i.e., the ability to encode, retain, and later realize an intention with a delay of minutes, hours or days. Behavioural and neurophysiological findings from both prospective and retrospective memory research suggest that the efficiency of encoding processes is reduced at both ends of the lifespan and that neural generators underlying successful encoding might differ in childhood and old age. Hence, the present study investigates compensational neural mechanisms during the encoding of intentions in adolescents and old adults compared to young adults.

Methods

We compared Event-Related Potentials (ERPs) and their source localization in 14 adolescents (11-13 years), 14 young adults (18-25 years), and 14 old adults (64-79 years) in a prospective memory task that was embedded in a semantic categorization task.

Results

Our data revealed three event-related modulations that differentiate between conditions (i.e., ongoing activity and successful intention formation trials) and groups. Source localizations of these modulations with standardized low-resolution electromagnetic tomography (sLORETA) revealed compensational activations in adolescents and old adults compared to young adults in successful intention formation trials: while adolescents showed a higher activation of secondary occipital regions in the time window of 500-1200 msec with a maximum around 800 msec, old adults activated prefrontal regions to a greater extent beginning at 700 msec, persisting until 1200 msec and expanding to middle temporal regions.

Conclusion

For a successful encoding of intentions adolescents and old adults recruit more neural generators than young adults. More importantly, the pattern of these compensational activations is different when comparing adolescents with young adults and old adults with young adults. These differences are discussed with regard to differential maturational changes in the brain.     

Involvement of hippocampal synaptic plasticity in age-related memory decline

This article examines the functional significance of Ca²⁺-dependent synaptic plasticity in relation to compromised memory function during aging. Research characterizing an age-related decline in memory for tasks that require proper hippocampal function is summarized. It is concluded that aged animals possess the mechanisms necessary for memory formation, and memory deficits, including rapid forgetting, result from more subtle changes in memory processes for memory storage or maintenance. A review of experimental studies concerning changes in hippocampal neural plasticity over the course of aging indicates that, during aging, there is a shift in mechanisms that regulate the thresholds for synaptic modification, including Ca²⁺ channel function and subsequent Ca²⁺-dependent processes. The results, combined with theoretical considerations concerning synaptic modification thresholds, provide the basis for a model of age-related changes in hippocampal synaptic function. The model is employed as a foundation for interpretation of studies examining therapeutic intervention in age-related memory decline. The possible role of altered synaptic plasticity thresholds in learning and memory deficits suggests that treatments that modify synaptic plasticity may prove fruitful for the development of early therapeutic interventions in age-related neurodegenerative diseases.